A retrospective observational study. This study investigated the clinical and radiological results of using cortical bone trajectory (CBT) screws versus traditional pedicle (TP) screws in transforaminal lumbar interbody fusion (TLIF) during a five-year follow-up of patients with single-level lumbar degenerative spondylolisthesis. Few studies have compared five-year follow-up outcomes between CBT screws and TP screws in TLIF. We reviewed outcome data of patients with single-level lumbar degenerative spondylolisthesis who underwent TLIF procedures with CBT screws (131 patients) or TP screws (80 patients) between 2011 and 2015. Patient-reported clinical outcome data included Oswestry disability index scores and visual analog scale (VAS) scores for back and leg pain at baseline, six months, and one year, two years, and five years postoperatively. The radiographic fusion rate and prevalence of secondary surgery for adjacent segment disease were also measured. During the follow-up over five years, the CBT group had significantly lower VAS scores for back pain ( P <0.0001, respectively). At two years after surgery, the CBT group had significantly higher VAS scores for leg pain ( P =0.007). At five years postoperatively, no significant differences existed in the VAS score for leg pain or in the Oswestry disability index score between the two groups. Radiographic fusion rates (CBT vs. TP: 95.5% vs. 95.9%; P =0.881) and adverse events during the five years after surgery were not significantly different. At two years postoperatively, the prevalence of secondary surgery to treat adjacent segment disease was significantly different between the two groups (CBT vs . TP: 13.7% vs. 5.0%; P =0.044). Our results suggest that, during a five-year followup, CBT screws for TLIF were an effective treatment compared to TP screws in the setting of single-level lumbar degenerative spondylolisthesis. However, when using CBT screws for TLIF, surgeons should consider the higher rate of secondary procedures to treat symptomatic adjacent segment disease.